A great deal of experimental effort has been directed toward understanding various aspects of B cell development. Early studies focused on the B cell receptor as the primary signal required for cell maturation, differentiation, and prolonged survival. Subsequent investigation has revealed that members of the tumor necrosis factor superfamily are required for complete development of B cells. Recently, TNF ligands, BLyS and APRIL, and TNF receptors, BAFF-R, BCMA, and TACI have been intensively studied because of evidence implicating them in normal B cell development. However, the primary focus of these studies has been in defining the role these molecules play in early B cell development. Thus, considerably less information is available concerning their role in later stages of B cell differentiation. Our preliminary data demonstrate that expression of B cell maturation antigen (BCMA) increases during B cell differentiation into antibody secreting cells. The precise role that BCMA plays during this process remains to be elucidated. Therefore, this proposal will specifically investigate the signals that regulate BCMA expression, the signals delivered by BCMA, and the role of BCMA in human B cell differentiation.